a study evaluating talazoparib (bmn 673), a parp inhibitor, in advanced and/or metastatic breast cancer patients with brca mutation (embraca study)

Conditions: Breast Neoplasms; BRCA 1 Gene Mutation; BRCA 2 Gene Mutation

Summary: the purpose of this open-label, 2:1 randomized phase iii trial is to compare the safety and efficacy of talazoparib (also known as bmn 673) versus protocol-specific physician's choice in patients who have locally advanced and/or metastatic breast cancer with germline brca mutations.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed carcinoma of the breast * locally advanced breast cancer that is not amenable to curative radiation or surgical cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapy * documentation of a deleterious, suspected deleterious, or pathogenic germline brca1 or brca2 mutation from myriad genetics or other laboratory approved by the sponsor * no more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies or targeted anticancer therapies such as mechanistic target of rapamycin (mtor) or cdk4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against ctl4 or vegf) * prior treatment with a taxane and/or anthracycline in the neoadjuvant, adjuvant, locally advanced, or metastatic setting unless medically contraindicated * have measurable or non-measurable, evaluable disease by the revised response evaluation criteria in solid tumors (recist) v.1.1 * eastern cooperative oncology group (ecog) performance status ≤ 2 exclusion criteria: * first-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy unless the investigator determines that one of the 4 cytotoxic chemotherapy agents in the control arm would otherwise be offered to the subject * prior treatment with a parp inhibitor (not including iniparib) * not a candidate for treatment with at least 1 of the treatments of protocol-specific physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine) * subjects who had objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease; subjects who received low-dose platinum therapy administered in combination with radiation therapy are not excluded * subjects who have received platinum in the adjuvant or neoadjuvant setting are eligible; however, subjects may not have relapsed within 6 months of the last dose of prior platinum therapy * cytotoxic chemotherapy within 14 days before randomization * radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days before randomization * her2 positive breast cancer * active inflammatory breast cancer * cns metastases * exception: adequately treated brain metastases documented by baseline ct or mri scan that has not progressed since previous scans and that does not require corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of cns symptoms. a repeat ct or mri following the identification of cns metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases. * subjects with leptomeningeal carcinomatosis are not permitted * prior malignancy except for any of the following: * prior brca-associated cancer as long as there is no current evidence of the cancer * carcinoma in situ or non-melanoma skin cancer * a cancer diagnosed and definitively treated ≥ 5 years before randomization with no subsequent evidence of recurrence * known to be human immunodeficiency virus positive * known active hepatitis c virus, or known active hepatitis b virus * known hypersensitivity to any of the components of talazoparib

Keywords: breast cancer brca mutation parp inhibitor brca 1 brca 2